Regulated activation of cell-membrane receptors by metal-chelating agonists

Abstract

Invented is a regulated activation of cell-membrane receptors by small molecule agents. Also invented is a method to render a cell-membrane receptor responsive to the activation by small molecule compounds by specific single point mutations in the transmembrane region.

What is claimed is:  
     
         1 . A DNA construct encoding a cell-membrane receptor, whose transmembrane domain has been modified with a single point mutation to His.  
     
     
         2 . A DNA construct encoding a cell-membrane receptor, whose transmembrane domain has been modified with point mutations to Thr and His.  
     
     
         3 . A DNA construct of  claim 2  where the Thr and His are three residues apart.  
     
     
         4 . A cell-membrane receptor encoded by a DNA construct of claims  1 - 3 .  
     
     
         5 . A genetically engineered cell containing and capable of expressing a DNA construct of claims  1 - 3 .  
     
     
         6 . A cell of  claim 5  containing a target gene under the expression control of a transcriptional control element responsive to the receptor of  claim 4 .  
     
     
         7 . A method for activating a cell-membrane receptor which comprises exposing the cells of  claim 5  with a metal-chelating receptor agonist.  
     
     
         8 . A method of  claim 7  wherein the cells are grown in a culture medium and the exposing is effected by adding the metal-chelating receptor agonist to the culture medium.  
     
     
         9 . A method of  claim 7  wherein the cells are present in a host organism and the exposing is effected by administering the metal-chelating receptor agonist to the host organism.  
     
     
         10 . A method of  claim 9  wherein the host organism is a mammal and the metal-chelating receptor agonist is administered in a therapeutically effective dose in a pharmaceutically acceptable carrier.  
     
     
         11 . A method of  claim 10  wherein the metal-chelating receptor agonist is administered orally.  
     
     
         12 . A method of  claim 10  wherein the metal-chelating receptor agonist is administered parenterally.  
     
     
         13 . A kit which comprises at least one DNA construct of any of claims  1 - 3 .  
     
     
         14 . A kit of  claim 13  which further comprises a metal-chelating receptor agonist.  
     
     
         15 . A host organism containing a cell of  claim 5 .  
     
     
         16 . A host organism of  claim 15  which is of mammalian origin.  
     
     
         17 . A mammal of  claim 16  which is of human origin.